Laquinimod sodium, also known as a sodium 5-chloro-3-(ethylphenylcarbamoyl)-1-methyl-2-oxo-1,2-dihydroquinolin-4-olate, ALLEGRO, ABR-215062 sodium or TV-5600 is a once-daily, orally administered immunomodulatory compound that was developed as a disease-modifying treatment for relapsing remitting multiple sclerosis (RRMS). Laquinimod has demonstrated potent therapeutic efficacy in preclinical and clinical models of other autoimmune diseases such as Crohn's disease, rheumatoid arthritis, insulin-dependent diabetes mellitus, Guillain Barré Syndrome, and Lupus.
Several patents, patent applications (U.S. Pat. No. 6,077,851, U.S. Pat. No. 6,875,869, U.S. Pat. No. 7,560,557, WO 2009/133468 and WO 2010/028015) and scientific publications (Jansson et al., J. Org. Chem. 2006, 71, 1658-1667; and Wennerberg et al., Organic Process Research & Development, 2007, 11, 674-680) disclose the compound Laquinimod, its pharmacological activity and processes for its preparation. The typical preparation scheme is summarized below (Scheme 1):

The aforementioned methods for Laquinimod synthesis are based on the intermediate 1,2-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxo-quinoline-3-carboxylic acid (6) and its alkyl(methyl)ester (5). The main disadvantage of such approaches is facile decarboxylation of acid (6) under basic and acidic conditions (see, Wennerberg et al.), that leads to a significant decrease in the yield of the final product and complicates the stage of final product purification and sodium salt formation. Even methyl ester (5) demands completely anhydrous conditions for handling. With this background, a synthetic sequence more suitable for large scale preparation of Laquinimod and other quinolin-3-carboxamide derivatives is desirable.